Project Summary From the earliest recognition of families with a high rate of cancer over 100 years ago, researchers have been focused on the genetic underpinnings of inherited cancers; however, identification remains a significant challenge due to persistent barriers across patient, provider and health system stakeholders, despite recent advances in the development of electronic medical records (EMR) and risk prediction tools that use family health history (FHH) information. Innovations in bioinformatic technology hold great promise in overcoming many of these barriers, particularly with the development of FHH applications that collect and analyze family data, and SMART-on-FHIR capabilities that can integrate third party apps with the EMR. MeTree, a patient facing risk assessment platform for 23 hereditary cancer syndromes with integrated education and evidence- based clinical decision support, is one such platform that served as the backbone of the Implementing Genomics in Practice (IGNITE) network's FHH clinical utility study, where it demonstrated improvements in the identification of those at risk, yet, also highlighted ongoing challenges particularly around undergoing genetic counseling and testing, and awareness of risk. We submit that these barriers can be overcome and that we can significantly improve identification and management of those at risk for hereditary cancer syndromes by bringing together a single clinical care platform that contains: a patient-facing risk assessment program integrated into the EMR, automated risk calculation with clinical decision support for patients and physicians for multiple hereditary cancer syndromes, systematic assessment of risk across a variety of clinic settings, guidance and education on family health history, genomics, risk management, and cascade screening, and an implementation sciences framework to allow us to build a novel and scalable clinical care paradigm for hereditary cancer risk assessment and risk management. To do this we will: 1) deploy a care delivery model that will facilitate systematic risk assessment for hereditary cancers in diverse clinical environments (in primary care and cancer care clinics at two different medical centers) in a randomized controlled trial of 4000 patients; 2) improve access to genetic healthcare providers for participants at risk for hereditary cancer syndromes by deploying the care delivery model in the cancer genetic counseling clinics in a randomized controlled trial of 300 patients; and 3) explore the feasibility of our care delivery model to improve family engagement for cancer risk assessment for patients who are found to have cancer gene variants or strong family histories of cancer. Wiesner GL and Orlando LA 1